TY - JOUR
T1 - Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats
AU - Dekker, N. A.M.
AU - van Meurs, M.
AU - van Leeuwen, A. L.I.
AU - van Slyke, P.
AU - Vonk, A. B.A.
AU - Boer, C.
AU - van den Brom, C. E.
PY - 2018
Y1 - 2018
N2 - Background: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. Methods: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. Results: CPB immediately impaired microcirculatory perfusion [5 (4–8) vs 10 (7–12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8–25) vs 7 (1–12) μg g−1, P=0.04] and lung [and 23 (13–60) vs 6 (4–16) μg g−1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6–28) μg g−1 vs 23 (13–60) μg g−1, P=0.04], but not in kidney [10 (3–23) vs 12 (8–25) μg g−1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. Conclusions: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.
AB - Background: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. Methods: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. Results: CPB immediately impaired microcirculatory perfusion [5 (4–8) vs 10 (7–12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8–25) vs 7 (1–12) μg g−1, P=0.04] and lung [and 23 (13–60) vs 6 (4–16) μg g−1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6–28) μg g−1 vs 23 (13–60) μg g−1, P=0.04], but not in kidney [10 (3–23) vs 12 (8–25) μg g−1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. Conclusions: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.
KW - capillary permeability
KW - cardiopulmonary bypass
KW - microcirculation
UR - http://www.scopus.com/inward/record.url?scp=85048730620&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bja.2018.05.049
DO - https://doi.org/10.1016/j.bja.2018.05.049
M3 - Article
C2 - 30336848
SN - 0007-0912
VL - 121
SP - 1041
EP - 1051
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 5
ER -